Sodium channel protein type 10 subunit alpha-Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1 complex (NaV1.8-MAGI1 complex)

The NaV1.8-MAGI1 complex is a functional protein assembly comprising the voltage-gated sodium channel NaV1.8 (encoded by SCN10A) and the scaffolding protein MAGI1 (Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1) [UniProt: Q9Y5Y9, Q96OT2]. NaV1.8 is primarily expressed in the nociceptive neurons of the dorsal root ganglia, where it plays a pivotal role in the initiation and maintenance of action potentials in response to painful stimuli [PubMed: 25153124]. The interaction is mediated by the C-terminal PDZ-binding motif of NaV1.8 and the PDZ domains of MAGI1, which is essential for the proper trafficking, membrane stabilization, and surface density of the channel [PubMed: 17434478]. This complex is a critical regulator of neuronal excitability, and its disruption or overactivity is strongly associated with chronic pain states, including neuropathic and inflammatory pain [PubMed: 30232205]. While current clinical candidates like Suzetrigine (VX-548) act as direct inhibitors of the NaV1.8 channel pore, the NaV1.8-MAGI1 interaction represents a novel therapeutic site for modulating channel function by targeting its regulatory scaffolding [ClinicalTrials.gov: NCT05086159]. Pharmacological modulation of this complex could potentially provide a more targeted approach to pain management with fewer side effects than non-selective sodium channel blockers.

Other names

SCN10A-MAGI1 complexNaV1.8-MAGI-1 complexSodium channel protein type 10 subunit alpha-MAGI1 complexNaV1.8-MAGI1 interaction

Voltage-gated sodium channel inhibition